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Here, we explore whether immunogenic cell death (ICD) marker ERp57 translocated from endoplasmic reticulum to cell surface after drug treatment could be used as a target for CAR-NK therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To target ERp57, a VHH phage display library was used for screening ERp57-targeted nanobodies (Nbs). A candidate Nb with high binding affinity to both human and mouse ERp57 was used for constructing CAR-NK cells. Various in vitro and in vivo studies were performed to assess the antitumor efficacy of the constructed CAR-NK cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We demonstrate that the translocation of ERp57 can not only be induced by low-dose oxaliplatin (OXP) treatment but also is spontaneously expressed on the surface of various types of tumor cell lines. Our results show that G6-CAR-NK92 cells can effectively kill various tumor cell lines in vitro on which ERp57 is induced or intrinsically expressed, and also exhibit potent antitumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the antitumor activity of G6-CAR-NK92 cells is synergistically enhanced by the low-dose ICD-inducible drug OXP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Collectively, our findings suggest that ERp57 can be leveraged as a new tumor antigen for CAR-NK targeting, and the resultant CAR-NK cells have the potential to be applied as a broad-spectrum immune cell therapy for various cancers by combining with ICD inducer drugs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-008888","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T11:40:34Z","timestamp":1720093234000},"page":"e008888","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Off-the-shelf CAR-NK cells targeting immunogenic cell death marker ERp57 execute robust antitumor activity and have a synergistic effect with ICD inducer oxaliplatin"],"prefix":"10.1136","volume":"12","author":[{"given":"Liuhai","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China"},{"name":"Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China"},{"name":"Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China"},{"name":"Department of Hematology, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangwei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China"},{"name":"Department of Neurosurgery & Medical Research Center, Shunde Hospital, Southern Medical University (The First People\u2019s Hospital of Shunde Foshan), Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; 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